It is now quite clear that human health is dependent at all times on the integrated function of a variety of systems that together constitute the immune system. This research offers an immunochemical approach to answering an important question in immunology: What were the phylogenetic origins of the immunoglobulins and how did they evolve? Immunoglobulin molecules are found in all vertebrate classes but in no known invertebrate. As one ascends the vertebrate phylogenetic tree the complexity of the immunoglobulin repertoire increases. In shark there is a single IgM-like antibody class; in man, five isotypes are recognized: IgM, IgD, IgG, IgA and IgE. Studies on mammalian immunoglobulins have resulted in predictions concerning the invertebrate origin and subsequent evolution of this great protein family. The basic theme is one of repeated duplications of an ancestral gene followed by divergent evolution and transposition of the genetic elements. The object of this research is to test the validity of these predictions by comparing degrees of amino acid sequence homology among the various immunoglobulins and precursor proteins. This comparison is based on polyclonal antisera directed against the sequential determinants exposed in denatured immunoglobulin chains. The significance of these studies is that they will provide: 1) a more complete description of immunoglobulin evolution in the vertebrates, 2) a probe to bridge the gap between vertebrates and invertebrates, and 3) a fund of information applicable to the understanding of the immune system.